SYNTHESIS OF 3,3-DIMETHYLAZETIDINE-2-CARBOXYLIC ACID AND SOME DERIVATIVES

gamma-Chloro-alpha-(N-alkylimino)esters were reduced by sodium cyanobo rohydride in methanol in the presence of acetic acid with complete sel ectivity to give rise to either gamma-chloro-alpha-(N-alkylamino)ester s (reaction at 0 degrees C) or 1-alkyl-3,3-dimethylazetidine-2-carboxy lic esters(reaction at reflux). The isolable gamma-chloro-alpha-(N-alk ylamino)esters are suitable sources for -alkylamino)-2,2-dimethylcyclo propane-1-carboxylic esters via base-induced 1,3-dehydrochlorination w hile the former substrates as transient species undergo 1,4-dehydrochl orination to the corresponding azetidines. The latter process was used for the synthesis of 3,3-dimethylazetidine-2-carboxylic acid, a new n on-proteinogenic sterically hindered alpha-amino acid, via hydrogenoly sis of methyl 1-benzyl-3,3-dimethylazetidine-1-carboxylate and subsequ ent acidic hydrolysis. Reduction of alkyl chloro-3,3-dimethyl-alpha-(N -alkylimino)butanoates with lithiumaluminiumhydride in diethyl ether a fforded 1-alkyl-3,3-dimethyl-2-(hydroxymethyl) azetidines. (C) 1998 El sevier Science Ltd. All rights reserved.